α‐Lactalbumin Peptide Asp‐Gln‐Trp Ameliorates Hepatic Steatosis and Oxidative Stress in Free Fatty Acids‐Treated HepG2 Cells and High‐Fat Diet‐Induced NAFLD Mice by Activating the PPARα Pathway

Scope Dietary intervention has emerged as a promising strategy for the management of nonalcoholic fatty liver disease (NAFLD). The aim of this study is to investigate the ameliorative effects of the α‐lactalbumin peptide Asp‐Gln‐Trp (DQW) against NAFLD and the underlying mechanism. Methods and results The models of lipid metabolism disorders are established both in HepG2 cells and in C57BL/6J mice. The results demonstrate that DQW activates peroxisome proliferator‐activated receptor α (PPARα) and subsequently ameliorates lipid deposition and oxidative stress in vitro. Interestingly, GW6471 markedly attenuates the modulatory effects of DQW on the PPARα pathway in HepG2 cells. Moreover, results of in vivo experiments indicate that DQW alleviates body weight gain, dyslipidemia, hepatic steatosis, and oxidative stress in high‐fat‐diet (HFD)‐induced NAFLD mice. At the molecular level, DQW activates PPARα, subsequently enhances fatty acid β‐oxidation, and reduces lipogenesis, thereby ameliorating hepatic steatosis. Meanwhile, DQW may ameliorate liver injury and oxidative stress via activating the PPARα/nuclear‐factor erythroid 2 (Nrf2)/heme‐oxygenase 1 (HO‐1) pathway. Conclusion Those results indicate that α‐lactalbumin peptide DQW may be an effective dietary supplement for alleviating NAFLD by alleviating lipid deposition and oxidative stress.